Process for the preparation of 2-chloro-5-chloromethyl-1,3-thiazole

ABSTRACT

According to the present invention, provided are 
     (1) a process for the preparation of 2-chloro-5-chloromethyl-1,3-thiazole, by reacting 3- chloro-1-isothiocyanato-1-propene with a chlorinating agent, 
     (2) a process for the preparation of 3-chloro-1-isocyanato-1-propene, by rearranging 3-chloro-1-thiocyanato-2-propene in the presence of a salt of one or more than one metal selected from the group consisting of metals belonging to Group 2A, Group 7A, Group 8 and Group 1B of the long-form periodic table, and 
     (3) a process for the preparation of 3-chloro-1-thiocyanato-2-propene, by reacting 1,3-dichloropropene and a thiocyanate salt 
     (a) in the presence of water, 
     (b) in the presence of an organic solvent which is water-soluble and has a boiling point of 150° C. or lower, or 
     (c) in an organic solvent in the presence of a phase transfer catalyst.

This application is a divisional of Ser. No. 09/225,292 filed Jan. 5,1999, U.S. Pat. No. 6,103,921 which is a divisional of Ser. No.08/804,401 filed Feb. 21, 1997, U.S. Pat. No. 5,894,073.

BACKGROUND OF THE INVENTION

1. Field of the Invention

This invention relates to a process for the preparation of2-chloro-5-chloromethyl-1,3-thiazole.2-Chloro-5-chloromethyl-1,3-thiazole prepared according to the presentinvention is useful as a synthesis intermediate for agriculturalchemicals, for example, as a synthesis intermediate forhexahydrotriazine compounds useful as insecticides (refer to JapanesePatent Publication No. HEI 6-776).

2. Discussion of the Background

As a preparation process of 2-chloro-5-chloromethyl-1,3-thiazole, knownare (1) a process of reacting allyl isothiocyanate with chlorine (referto Japanese Patent Application Laid-Open No. SHO 63-83079) and (2) aprocess of reacting 2-chloroallyl isothiocyanate with a chlorinatingagent (refer to Japanese Patent Application Laid-Open No. HEI 4-234864).

The reaction described in the above process (1) is however a markedlysevere reaction which requires a large excess amount of a chlorinatingagent and high temperature and in addition, plural byproducts are formedtogether with the target product 2-chloro-5-chloromethyl-1,3-thiazole sothat this process is accompanied by the problem that2-chloro-5-chloromethyl-1.3-thiazole so obtained has low purity. On theother hand, the process described in the above (2) is also accompaniedwith the problem that 2-chloroallyl isothiocyanate, which is a startingmaterial, is not available at low cost. Accordingly, it is difficult tosay that each of these processes is an industrially excellent processfor the preparation of 2-chloro-5-chloromethyl-1,3-thiazole.

In addition, a process of heating 3-chloro-1-thiocyanato-2-propene indioxane is known as a process for the preparation of3-chloro-1-isothiocyanato-1-propene (refer to Journal f. prakt. Chemie.322(4), 629(1980)).

It is however known that the above process has a low yield (refer toComparative Example 2 which will be described below) and dioxane whichis used as a solvent is carcinogenic. Accordingly, it is difficult tosay that this process is industrially advantageous for the preparationof 3-chloro-1-isothiocyanato-1-propene.

Furthermore, as a process for the preparation of3-chloro-1-thiocyanato-2-propene, a process of reacting1,3-dichloropropene and potassium thiocyanate in dimethyl sulfoxide isshown (refer to Journal f. prakt. Chemie. 322(4), 629(1980)).

The above process however has a yield as low as 47% so that it isdifficult to say that it is an industrially advantageous process for thepreparation of 3-chloro-1-thiocyanato-2-propene.

With respect to the processes described in the above (1) and (2),isolation and purification of 2-chloro-5 -chloromethyl-1,3-thiazole arecarried out by distillation.

Since 2-chloro-5-chloromethyl-1,3-thiazole has low thermal stability andits reflux ratio cannot be increased,2-chloro-5-chloromethyl-1,3-thiazole purified by distillation has a lowpurity. It is difficult to say that distillation is an excellentpurification method for 2-chloro-5-chloromethyl-1,3-thiazole.Accordingly, there is a demand for a purification method to obtain2-chloro-5-chloromethyl-1,3-thiazole having a higher purity.

SUMMARY OF THE INVENTION

An object of the present invention is to provide an industriallyadvantageous process for preparing 2-chloro-5-chloromethyl-1,3-thiazoleunder mild conditions using an easily available and inexpensive startingmaterial without using a large excess amount of a chlorinating agent.

Another object of the present invention is to provide an industriallyadvantageous process for the preparation of3-chloro-1-isothiocyanato-1-propene in high purity and in high yield.

A further object of the present invention is to provide an industriallyadvantageous process for the preparation of3-chloro-1-thiocyanato-2-propene in high purity and in high yield.

A still further object of the present invention is to provide a processfor the purification of 2-chloro-5-chloromethyl-1,3-thiazole with goodpurity.

In a first aspect of the present invention, there is thus provided aprocess for the preparation of 2-chloro-5-chloromethyl-1,3-thiazole,which comprises reacting 3-chloro-1-isothiocyanato-1-propene with achlorinating agent.

In a second aspect of the present invention, there is also provided aprocess for the preparation of 2-chloro-5-chloromethyl-1,3-thiazole,which comprises rearranging 3-chloro-1-thiocyanato-2-propene in thepresence of a salt of one or more than one metal selected from the groupconsisting of metals belonging to Group 2A, Group 7A, Group 8 and Group1B of the long-form periodic table to obtain3-chloro-1-isothiocyanato-1-propene; and reacting the3-chloro-1-isothiocyanato-1-propene with a chlorinating agent.

In a third aspect of the present invention, there is also provided aprocess for the preparation of 3-chloro-1-isothiocyanato-1-propene,which comprises rearranging 3-chloro-1-thiocyanato-2-propene in thepresence of a salt of one or more than one metal selected from the groupconsisting of metals belonging to Group 2A, Group 7A, Group 8 and Group1B of the long-form periodic table.

In a fourth aspect of the present invention, there is also provided aprocess for the preparation of 2-chloro-5-chloromethyl-1,3-thiazole,which comprises reacting 1,3-dichloropropene and a thiocyanate salt

(a) in the presence of water,

(b) in the presence of an organic solvent which is water-soluble and hasa boiling point of 150° C. or lower, or

(c) in an organic solvent in the presence of a phase transfer catalyst,to obtain 3-chloro-1-thiocyanato-2-propene;

rearranging the 3-chloro-1-thiocyanato-2-propene in the presence of asalt of one or more than one metal selected from the group consisting ofmetals belonging to Group 2A, Group 7A, Group 8 and Group 1B of thelong-form periodic table to obtain 3-chloro-1-isothiocyanato-1-propene;and reacting the 3-chloro-1-isothiocyanato-1-propene with a chlorinatingagent.

In a fifth aspect of the present invention, there is also provided aprocess for the preparation of 3-chloro-1-isothiocyanato-1-propene,which comprises reacting 1,3-dichloropropene and a thiocyanate salt

(a) in the presence of water,

(b) in the presence of an organic solvent which is water-soluble and hasa boiling point of 150° C. or lower, or

(c) in an organic solvent in the presence of a phase transfer catalyst,to obtain 3-chloro-1-thiocyanato-2-propene; and rearranging the3-chloro-1-thiocyanato-2-propene in the presence of a salt of one ormore than one metal selected from the group consisting of metalsbelonging to Group 2A, Group 7A, Group 8 and Group 1B of the long-formperiodic table.

In a sixth aspect of the present invention, there is also provided aprocess for the preparation of 3-chloro-1-thiocyanato-2-propene, whichcomprises reacting 1,3-dichloropropene and a thiocyanate salt

(a) in the presence of water,

(b) in the presence of an organic solvent which is water-soluble and hasa boiling point of 150° C. or lower, or

(c) in an organic solvent in the presence of a phase transfer catalyst.

In a seventh aspect of the present invention, there is also provided aprocess for the purification of 2-chloro-5-chloromethyl-1,3-thiazole,which comprises recrystallizing crude2-chloro-5-chloromethyl-1,3-thiazole using one or more than one organicsolvent selected from the group consisting of hydrocarbons, ethers,aldehydes, ketones, esters and alcohols.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

Each of the preparation processes of the present invention willhereinafter be described specifically.

Process 1

A process to obtain 3-chloro-1-thiocyanato-2-propene by reacting1,3-dichloropropene and a thiocyanate salt

(a) in the presence of water,

(b) in the presence of an organic solvent which is water-soluble and hasa boiling point of 150° C. or lower, or

(c) in an organic solvent in the presence of a phase transfer catalyst:

Examples of the thiocyanate salts include alkali metal salts such assodium thiocyanate and potassium thiocyanate; alkaline earth metal saltssuch as calcium thiocyanate and magnesium thiocyanate; and ammoniumthiocyanate. Among them, sodium thiocyanate is preferred. It is desiredthat the thiocyanate is used in an amount of 1.0 to 1.5 moles per moleof 1,3-dichloropropene.

Process 1-(a)

In the case where 1,3-dichloropropene and a thiocyanate salt are reactedin the presence of water:

It is preferred that the amount of water which is allowed to exist inthe reaction system is 0.5 to 10 times the weight of1,3-dichloropropene, with 0.5 to 2.0 times being more preferred.

The reaction can be performed in the presence of a phase transfercatalyst. Examples of the catalyst include quaternary ammonium salts andquaternary phosphonium salts. Among them, tetraalkylammonium halidessuch as tetramethylammonium chloride, benzyltrimethylammonium chlorideand tetrabutylammonium chloride are preferred. It is desired that thephase transfer catalyst is used in an amount of 0.001 to 0.01 mole permole of 1,3-dichloropropene.

The reaction can be performed either in the presence of a solvent or ina solventless manner. No particular limitation is imposed on the solventinsofar as it does not adversely affect the reaction. Examples includehydrocarbons such as benzene, toluene, hexane, heptane and octane;halogenated hydrocarbons such as dichloromethane, chloroform, carbontetrachloride, 1,2-dichloroethane and 1,1,2,2-tetrachloroethane; andethers such as diethyl ether, diisopropyl ether and dimethoxyethane. Itis preferred that the solvent is used in an amount of 0.5 to 10 timesthe weight of 1,3-dichloropropene, with 1.0 to 2.0 times being morepreferred.

The preferred reaction temperature falls within a range of from 0° C. to150° C., with 20° C. to 80° C. being more preferred. The reaction timediffers depending on the reaction conditions, however, 1 to 4 hours aregenerally suitable.

Process I-(b)

In the case where 1,3-dichloropropene and a thiocyanate salt are reactedin the presence of an organic solvent which is water-soluble and has aboiling point of 150° C. or lower:

In the case where an organic solvent which is not water-soluble is usedsingly, 3-chloro-1-thiocyanato-2-propene cannot be obtained in a highyield (refer to Comparative Example I which will be described below). Inaddition, when an organic solvent which has a boiling point higher than150° C., for example, dimethyl sulfoxide (having a boiling point ofabout 160° C.) is used singly, the yield of the target product is as lowas 47% (refer to Journal f. prakt. Chemie. 322(4), 629(1980)).

Examples of the organic solvent which is water-soluble and has a boilingpoint of 150° C. or lower include nitriles such as acetonitrile andpropionitrile; alcohols such as methanol, ethanol and propanol; andketones such as acetone. These solvents may be used in combination. Itis more preferred that the boiling point of the solvent is 100° C. orlower. It is preferred that the solvent is used in an amount of 0.5 to10 times the weight of the thiocyanate salt, with 1.0 to 2.0 times beingmore preferred.

The reaction temperature preferably ranges from 0° C. to 150° C., with20° C. to 80° C. being more preferred. The reaction time differsdepending on the reaction conditions, however, the reaction time of 1 to4 hours is generally suitable.

Process 1-(c)

In the case where 1,3-dichloropropene and a thiocyanate salt are reactedin an organic solvent in the presence of a phase transfer catalyst:

No particular limitation is imposed on the organic solvent usable in thepresent invention insofar as it does not adversely affects the reaction.Examples include hydrocarbons such as benzene, toluene, hexane, heptaneand octane; halogenated hydrocarbons such as dichloromethane,chloroform, carbon tetrachloride, 1,2-dichloroethane and1,1,2,2-tetrachloroethane; ethers such as diethyl ether, diisopropylether, dimethoxyethane and tetrahydrofuran; ketones such as acetone,methyl ethyl ketone and cyclohexanone; nitriles such as acetonitrile andpropionitrile; alcohols such as methanol, ethanol and propanol; anddimethyl sulfoxide. It is preferred that the organic solvent is used inan amount of 0.5 to 10 times the weight of the thiocyanate salt, with1.0 to 2.0 times being more preferred. Alternatively, it is alsopossible to use 1,3-dichloropropene, which is a reaction substrate, inan excess amount in order to let it serve as a solvent in addition.

Such a reaction is carried out in the presence of a phase transfercatalyst. The use of the phase transfer catalyst makes it possible toprepare 3-chloro-1-thiocyanato-2-propene in high yield. For example, inthe case where dimethyl sulfoxide is used as a solvent, if the phasetransfer catalyst is not employed, the yield is 47%, while it rises evento 70% by the use of the phase transfer catalyst (refer to Journal f.prakt. Chemie. 322(4), 629(1980) and also Example 8 which will bedescribed below). When diisopropyl ether is used as a solvent, reactionhardly proceeds without the use of the phase transfer catalyst, but theyield rises even to 82% by the use of the phase transfer catalyst (referto Example 6 and Comparative Example 1 which will be described below).

Examples of the phase transfer catalyst include quaternary ammoniumsalts and quaternary phosphonium salts. Among them, tetramethylammoniumchloride, tetraethylammonium chloride, tetrabutylammonium chloride andbenzyltrimethylanunonium chloride are preferred. It is generallysuitable that the phase transfer catalyst is used in an amount of 0.001to 0.01 mole per mole of 1,3-dichloropropene.

The reaction temperature preferably falls within a range of from 0° C.to 150° C., with a range of from 20° C. to 80° C. being more preferred.The reaction time differs depending on the reaction conditions but thatof 1 to 4 hours is generally suitable.

The isolation and purification of 3-chloro-1-thiocyanato-2-propene fromthe reaction mixture are effected in a manner known per se in the art.For example, after being cooled, the reaction mixture is extracted withan organic solvent such as toluene, diethyl ether, methylene chloride,ethyl acetate or the like. The extract is then washed with saturatedsaline, dried and concentrated under reduced pressure. The resultingconcentrate is then isolated and purified by distillation under reducedpressure or chromatography or similar means. Alternatively,3-chloro-1-thiocyanato-2-propene can be provided for the subsequentreaction without being isolated and purified from the reaction mixture.

Incidentally, 1,3-dichloropropene which is employed as a startingmaterial is mass produced as an insecticide so that it is easilyavailable at a low cost.

Process 2

A process to obtain 3-chloro-1-isothiocyanato-1-propene by rearranging3-chloro-1-thiocyanato-2-propene in the presence of a salt of one ormore than one metal selected from the group consisting of metalsbelonging to Group 2A, Group 7A, Group 8 and Group 1B of a long-formperiodic table:

Examples of the metal salt usable in such a reaction include salts of ametal belonging to Group 2A, Group 7A, Group 8 or Group 1B of along-form periodic table. Examples of the metal belonging to Group 2Ainclude magnesium, calcium and barium; those of the metal belonging toGroup 7A include manganese; those of the metal belonging to Group 8include iron, ruthenium, cobalt, rhodium, nickel, palladium andplatinum; and those of the metal belonging to Group 1B include copper,silver and gold.

These metals are used in the form of a metal salt. Examples of the metalsalt include halides such as chloride, bromide and iodide; inorganicsalts such as sulfate, nitrate, phosphate, hydroxide, carbonate andthiocyanate; organic salts such as acetate, benzoate andacetylacetonate; and oxides.

Specific examples of the metal salt include magnesium salts such asmagnesium chloride, magnesium bromide, magnesium sulfate, magnesiumoxide and magnesium acetate; manganese salts such as manganese chloride;iron salts such as ferrous (or ferric) sulfate and ferrous (or ferric)nitrate; ruthenium salts such as ruthenium chloride; cobalt salts suchas cobalt chloride, cobalt bromide, cobalt sulfate and cobalt acetate;nickel salts such as nickel chloride and nickel bromide; palladium saltssuch as palladium chloride and palladium acetate; and copper salts suchas copper (I) chloride, copper (II) chloride, copper sulfate, copperthiocyanate, copper (I) oxide, copper (II) oxide, copper acetate andcopper acetylacetonate. A better yield can be obtained when magnesiumchloride, cobalt chloride or copper (II) chloride is used among theabove-exemplified metal salts. These metal salts can be used eithersingly or in combination.

It is preferred that the metal salt is used in an amount falling withina range of from 0.01 to 0.1 mole per mole of3-chloro-1-thiocyanato-2-propene.

Such a reaction can be carried out either in the presence of a solventor in a solventless manner. No particular limitation is imposed on thesolvent to be employed insofar as it does not adversely affect thereaction. Examples include hydrocarbons such as toluene, xylene, hexane,heptane and octane; halogenated hydrocarbons such as dichloromethane,chloroform, carbon tetrachloride, 1,2-dichloroethane and1,1,2,2-tetrachloroethane; ethers such as diethyl ether, diisopropylether and dimethoxyethane; nitriles such as acetonitrile andpropionitrile; and amides such as dimethyl formamide. It is preferredthat the solvent is used in an amount of 1 to 50 times the weight of3-chloro-1-thiocyanato-2-propene, with 4 to 20 times being morepreferred.

The reaction temperature preferably falls within a range of from 0° C.to 200° C., with a range of from 100° C. to 150° C. being morepreferred. The reaction time differs depending on the reactionconditions but that of 0.5 to 5 hours is generally suitable.

The isolation and purification of 3-chloro-1-isothiocyanato-1-propenefrom the resulting reaction mixture are carried out in a manner knownper se in the art.

Described specifically, after cooling the reaction mixture, the metalsalt is removed therefrom by filtration. The filtrate is thenconcentrated under reduced pressure. The resulting concentrate is thenisolated and purified by distillation under reduced pressure orchromatography or the like means. Alternatively,3-chloro-1-isothiocyanato-1-propene can be provided for the subsequentreaction without isolation and purification from the reaction mixture.

Process 3

A process to obtain 2-chloro-5-chloromethyl-1,3-thiazole by reacting3-chloro-1-isothiocyanato-1-propene with a chlorinating agent:

Such a reaction can be carried out either in the presence of a solventor in a solventless manner. No particular limitation is imposed on thesolvent to be employed insofar as it does not adversely affect thereaction. Examples include halogenated hydrocarbons such asdichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethaneand 1,1,2,2-tetrachloroethane; hydrocarbons such as benzene, toluene,hexane, heptane and octane; ethers such as diethyl ether, diisopropylether, tetrahydrofuran, dioxane and dimethoxyethane; nitriles such asacetonitrile and propionitrile; amides such as dimethylformamide; anddimethyl sulfoxide. It is preferred that the solvent is used in anamount of 0.5 to 10 times the weight of3-chloro-1-isothiocyanato-1-propene, with 0.5 to 2.0 times being morepreferred.

As the chlorinating agent to be employed for the reaction, chlorine or acompound which emits chlorine under the reaction conditions, forexample, sulfuryl chloride can be used. From the viewpoint of the yield,sulfuryl chloride is preferred. It is preferred that the chlorinatingagent is used generally in an amount falling within a range of from 1.0equivalent to 1.5 equivalents relative to3-chloro-1-isothiocyanato-1-propene. In the case where chlorine is usedas the chlorinating agent, on the other hand, it is possible tointroduce a chlorine gas directly into the reaction system or to usechlorine dissolved in a solvent. As such a solvent, theabove-exemplified ones can be used.

The reaction temperature preferably falls within a range of from −20° C.to 150° C., with a range of from 0° C. to 60° C. being more preferred.The reaction time differs depending on the reaction conditions but thatof 1 to 4 hours is generally suitable.

In Process 3, it is preferred to usetrans-3-chloro-1-isothiocyanato-1-propene as a starting material sinceuse of this compound makes it possible to provide the target compound ina high yield. Trans-3-chloro-1-isothiocyanato-1-propene can be obtainedby distilling and separating 3-chloro-1-isothiocyanato-1-propene whichis a mixture of a cis-form and a trans-form. The cis-form separated herecan be converted into the trans-form by isomerization. Alternatively, itis possible to use a mixture of the cis-form and trans-form of3-chloro-1-isothiocyanato-1-propene as the starting material withoutisolating the trans-form in advance and to carry out the reaction of thepresent invention while isomerizing the cis-form into the trans-form.The cis-form can be isomerized into the trans-form in the presence of acatalyst generally used for the isomerization of a double bond. Examplesof such a catalyst include iodine; thiols such as thiophenol; and Lewisacids.

Incidentally, the use of magnesium chloride as a metal salt in thereaction of Process 2 makes it possible to provide trans-rich3-chloro-1-isothiocyanato-1-propene and is therefore preferred.

The isolation and purification of 2-chloro-5-chloromethyl-1,3-thiazolefrom the reaction mixture so obtained are carried out in a manner knownper se in the art. Described specifically, after being cooled, thereaction mixture is poured in an alkaline aqueous solution such assodium bicarbonate, sodium carbonate or sodium hydroxide. The resultingmixture is extracted with chloroform or the like. The extract is washedwith water, dried and then concentrated under reduced pressure. Theconcentrate is then isolated and purified by chromatography or similarmeans.

Process 4

A process of recrystallizing crude 2-chloro-5-chloromethyl-1,3-thiazoleusing one or more than one organic solvent selected from the groupconsisting of hydrocarbons, ethers, aldehydes, ketones, esters andalcohols:

A description will next be made of the organic solvent used for such apurification process. Examples of the hydrocarbons include aliphatichydrocarbons such as pentane, hexane, heptane and octane; aromatichydrocarbons such as benzene, toluene and xylene; and halogenatedhydrocarbons such as methylene chloride, chloroform and carbontetrachloride. Examples of the ethers include diethyl ether, diisopropylether and 1,2-dimethoxyethane. Examples of the aldehydes includepropionaldehyde and isobutyl aldehyde. Examples of the ketones includeacetone, methyl ethyl ketone and methyl isobutyl ketone. Examples of theesters include ethyl acetate and butyl acetate. Examples of the alcoholsinclude methanol, ethanol, propanol and butanol. It is preferred thatthe solvent is used in an amount of 0.5 to 20 times the weight of thecrude 2-chloro-5-chloromethyl-1,3-thiazole, with 1 to 5 times being morepreferred.

The crystallization temperature preferably falls within a range of −50°C. to 30° C., with a range of −30° C. to 0° C. being more preferred.

No particular limitation is imposed on the preparation process of thecrude 2-chloro-5-chloromethyl-1,3-thiazole usable in the presentinvention. Examples of the preparation process of the crude2-chloro-5-chloromethyl-1,3-thiazole include a process of the presentinvention, a process of reacting allyl isothiocyanate with chlorine(refer to Japanese Patent Application Laid-Open No. SHO 63-83079) and aprocess of reacting 2-chloroallyl isothiocyanate with a chlorinatingagent (refer to Japanese Patent Application Laid-Open No. HEI 4-234864).

The reaction concentrate, distillate or the like so obtained can beprovided for the purification process of the present invention.

EXAMPLES

The present invention will hereinafter be described more specifically byexamples. It should however be borne in mind that the present inventionis not limited to or by the following examples. Percentages are given inweight percent.

PROCESS 1

Example 1

In 250 ml of water, 200 g of sodium thiocyanate were dissolved. To theresulting solution, 250 g of 1,3-dichloropropene and 2.5 g oftetrabutylammonium chloride were added, followed by heating at 60° C.for 3 hours. The reaction mixture was cooled down to room temperatureand poured in 200 ml of water, followed by extraction with 500 ml ofxylene once. The organic layer was washed with 500 ml of saturatedsaline, dried over anhydrous sodium sulfate and then concentrated underreduced pressure. The concentrate was subjected to distillation underreduced pressure, whereby 258.0 g of 3-chloro-1-thiocyanato-2-propenewere obtained.

Yield: 84.1%

Purity: 98.1%

Boiling point: 83-88° C./5 mmHg

¹H-NMR spectrum (CDCl₃) δ:

3.59(d,J=7.8 Hz,(trans)), 3.80(d,J=7.0 Hz,(cis)),

6.04(dt,J=7.0 Hz,7.0 Hz,(cis)),

6.06(dt,J=14.0 Hz,7.8 Hz,(trans)),

6.39(d,J=14.0 Hz,(trans)), 6.42(d,J=7.0 Hz,(cis)).

Example 2

In 250 ml of water, 200 g of sodium thiocyanate were dissolved. To theresulting solution, 250 g of 1,3-dichloropropene were added, followed byheating at 60° C. for 6 hours. The reaction mixture was cooled down toroom temperature and poured in 200 ml of water, followed by extractionwith 500 ml of xylene once. The organic layer was washed with 500 ml ofsaturated saline, dried over anhydrous sodium sulfate and thenconcentrated under reduced pressure. The concentrate was subjected todistillation under reduced pressure, whereby 241.8 g of3-chloro-1-thiocyanato-2-propene were obtained.

Yield: 78.6%

Purity: 97.8%

Boiling point: 84-88° C./5 mmHg

Example 3

In 12 ml of acetonitrile, 2.14 g of sodium thiocyanate were dissolved.To the resulting solution, 2.66 g of 1,3-dichloropropene were added,followed by heating for 3 hours at the reflux temperature (80-82° C.) ofacetonitrile. The reaction mixture was cooled down to room temperatureand acetonitrile was distilled off under reduced pressure. After theaddition of 20 ml of water to the residue, the resulting mixture wasextracted twice with 20 ml of ethyl acetate. The organic layer waswashed with 20 ml of saturated saline, dried over anhydrous sodiumsulfate and then concentrated under reduced pressure. The concentratewas then purified by distillation under reduced pressure, whereby 2.89 gof 3-chloro-1-thiocyanato-2-propene were obtained.

Yield: 88.4%

Purity: 98.1%

Boiling point: 83-88° C./5 mmHg

Example 4

In 12 ml of methanol, 2.14 g of sodium thiocyanate were dissolved. Tothe resulting solution, 2.66 g of 1,3-dichloropropene were added,followed by heating for 3 hours at the reflux temperature (64-66° C.) ofmethanol. The reaction mixture was cooled down to room temperature andmethanol was distilled off under reduced pressure. After the addition of20 ml of water to the residue, the resulting mixture was extracted twicewith 20 ml of ethyl acetate. The organic layer was washed with 20 ml ofsaturated saline, dried over anhydrous sodium sulfate and thenconcentrated under reduced pressure. The concentrate was then purifiedby distillation under reduced pressure, whereby 2.86 g of3-chloro-1-thiocyanato-2-propene were obtained.

Yield: 87.6%

Purity: 98.2%

Boiling Point: 84-88° C./5 mmHg

Example 5

In 12 ml of acetone, 2.14 g of sodium thiocyanate were dissolved. To theresulting solution, 2.66 g of 1,3-dichloropropene were added, followedby heating for 5 hours at the reflux temperature (55-58° C.) of acetone.The reaction mixture was cooled down to room temperature and acetone wasdistilled off under reduced pressure. After the addition of 20 ml ofwater to the residue, the resulting mixture was extracted twice with 20ml of ethyl acetate. The organic layer was washed with 20 ml ofsaturated saline, dried over anhydrous sodium sulfate and thenconcentrated under reduced pressure. The concentrate was then purifiedby distillation under reduced pressure, whereby 2.72 g of3-chloro-1-thiocyanato-2-propene were obtained.

Yield: 83.1%

Purity: 97.9%

Boiling point: 83-88° C./5 mmHg

Example 6

To 12 ml of diisopropyl ether, 2.14 g of sodium thiocyanate, 2.66 g of1,3-dichloropropene and 33 mg of tetraethylammonium chloride were added.The resulting mixture was heated for 3 hours at the reflux temperature(68-70° C.) of diisopropyl ether. The reaction mixture was cooled downto room temperature and the salts so precipitated were filtered. Thefiltrate was washed with 20 ml of saturated saline, dried over anhydroussodium sulfate and then concentrated under reduced pressure. Theconcentrate was then purified by distillation under reduced pressure,whereby 2.71 g of 3-chloro-1-thiocyanato-2-propene were obtained.

Yield: 82.7%

Purity: 97.9%

Boiling point: 83-88° C./5 mmHg

Example 7

To 20 ml of toluene, 2.14 g of sodium thiocyanate, 2.66 g of1,3-dichloropropene and 43 mg of tetrabutyl ammonium chloride wereadded. The resulting mixture was heated for 5 hours at the refluxtemperature (110-115° C.) of toluene. The reaction mixture was cooleddown to room temperature, followed by the addition of 20 ml of water todissolve the resulting salts therein. The organic layer was separated,washed with 20 ml of saturated saline, dried over anhydrous sodiumsulfate and concentrated under reduced pressure. The concentrate waspurified by distillation under reduced pressure, whereby 2.59 g of3-chloro-1-thiocyanato-2-propene were obtained.

Yield: 78.6%

Purity: 97.4%

Boiling point: 83-88° C./5 mmHg

Example 8

To 20 ml of dimethyl sulfoxide, 2.14 g of sodium thiocyanate, 2.66 g of1,3-dichloropropene and 43 mg of tetrabutylammonium chloride were added,followed by the reaction at 25-30° C. for 3 hours. To the reactionmixture, 100 ml of water and 100 ml of isopropyl ether were added andthey were stirred. The reaction mixture was then allowed to stand toseparate the organic layer. The organic layer so obtained was washedwith 50 ml of saturated saline, dried over anhydrous sodium sulfate andconcentrated under reduced pressure. The concentrate was then purifiedby distillation under reduced pressure, whereby 2.41 g of3-chloro-1-thiocyanato-2-propene were obtained.

Yield: 73.0%

Purity: 97.2%

Boiling point: 83-88° C./5 mmHg

Comparative Example 1

To 12 ml of diisopropyl ether, 2.14 g of sodium thiocyanate and 2.66 gof 1,3-dichloropropene were added, followed by reaction for 7 hours atthe reflux temperature (68-70° C.) of diisopropyl ether. The reactionhardly proceeded and only a trace amount of3-chloro-1-thiocyanato-2-propene was obtained.

PROCESS 2

Example 9

A mixture of 198 g of 3-chloro-1-thiocyanato-2-propene, 1375 ml ofxylene and 9.35 g of copper (II) chloride was heated for one hour at thereflux temperature of xylene. The reaction mixture was cooled down toroom temperature and the copper salt was removed by filtration. Thefiltrate was concentrated under reduced pressure. The concentrate wassubjected to distillation under reduced pressure, whereby 184.0 g of3-chloro-1-isothiocyanato-1-propene were obtained.

Yield: 90.7%

Purity: 97.6%

Boiling point: 60-75° C./5 mmHg

¹H-NMR spectrum (CDCl₃)δ:

4.06(d,J=5.7 Hz,(trans)), 4.18(d,J=7.4 Hz,(cis))

5.60(dt,J=8.1 Hz,5.7 Hz,(cis)),

5.92(dt,J=13.5 Hz,7.4 Hz,(trans)),

6.15(d,J=8.1 Hz,(cis)), 6.27(d,J=13.5 Hz,(trans)).

Example 10

A mixture of 1.34 g of 3-chloro-1-thiocyanato-2-propene, 5 ml of tolueneand 0.20 g of copper (I) chloride was heated for 4 hours at the refluxtemperature of toluene. The reaction mixture was cooled down to roomtemperature and the copper salt was removed by filtration. The filtratewas concentrated under reduced pressure. The concentrate was subjectedto distillation under reduced pressure, whereby 1.23 g of3-chloro-1-isothiocyanato-1-propene were obtained.

Yield: 90.0%

Purity: 98.0%

Boiling point: 62-75° C./5 mmHg

Example 11

A mixture of 6.70 g of 3-chloro-1-thiocyanato-2-propene, 25 ml oftoluene and 0.33 g of magnesium chloride was heated at the refluxtemperature of toluene for 4 hours. The reaction mixture was cooled downto room temperature and the magnesium salt was removed by filtration.The filtrate was concentrated under reduced pressure. The concentratewas subjected to distillation under reduced pressure, whereby 6.10 g of3-chloro-1-isothiocyanato-1-propene were obtained.

Yield: 89.8%

Purity: 98.6%

Boiling point: 63-75° C./5 mmHg

Example 12

A mixture of 6.70 g of 3-chloro-1-thiocyanato-2-propene, 25 ml oftoluene and 0.33 g of cobalt chloride was heated at the refluxtemperature of toluene for 4 hours. The reaction mixture was cooled downto room temperature and the cobalt salt was removed by filtration. Thefiltrate was concentrated under reduced pressure. The concentrate wassubjected to distillation under reduced pressure, whereby 5.96 g of3-chloro-1-isothiocyanato-1-propene were obtained.

Yield: 87.6%

Purity: 98.5%

Boiling point: 62-75° C./5 mmHg

Comparative Example 2

A mixture of 1.34 g of 3-chloro-1-thiocyanato-2-propene and 5 ml ofdioxane was heated at the reflux temperature of dioxane for 6 hours. Thereaction mixture was cooled down to room temperature and concentratedunder reduced pressure. The concentrate was subjected to distillationunder reduced pressure, whereby 0.73 g of3-chloro-1-isothiocyanato-1-propene was obtained.

Yield: 51.8%

Purity: 95.0%

Boiling point: 64-75° C./5 mmHg

PROCESS 3

Example 13

In a reaction vessel, 26.8 g of 3-chloro-1-isothiocyanato-1-propene (a2:3 mixture of cis-form and trans form) and 30 ml of chloroform werecharged, followed by cooling to 0° C. While the internal temperature waskept at 10° C. or lower, 28.0 g of sulfuryl chloride were added dropwiseto the resulting mixture over one hour. After the completion of thedropwise addition, the temperature was increased up to 50-60° C. andheating was carried out at the same temperature for 3 hours. Thereaction mixture was cooled down to room temperature and then pouredinto 350 ml of a 10% aqueous solution of sodium carbonate. Then, theresulting mixture was extracted with 100 ml of chloroform twice. Theorganic layer was washed twice with 100 ml of saturated saline and driedover anhydrous sodium sulfate. The solvent was then distilled off,whereby 35.2 g of the crude reaction product were obtained. The crudereaction product was purified by distillation under reduced pressure,whereby 24.9 g of 2-chloro-5-chloromethyl-1,3-thiazole were obtained.

Yield: 69.2%

Purity: 93.8%

Boiling point: 107-109° C./17 mmHg

¹H-NMR spectrum (CDCl₃)δ:

4.72(s,2H), 7.50(s,1H).

Example 14

In a reaction vessel, 26.8 g of 3-chloro-1-isothiocyanato-1-propene (a2:3 mixture of cis-form and trans-form) and 30 ml of chloroform werecharged, followed by cooling to 0° C. While the internal temperature waskept at 10° C. or lower, chlorine gas was introduced into the reactionmixture over 1.5 hours. The chorine gas was used in an amount of 22.3 g.After the completion of the reaction was confirmed, bubbling of nitrogengas was effected to remove the excess chlorine gas and hydrogen chloridegas. The reaction mixture was poured in 350 ml of a 10% aqueous solutionof sodium carbonate, followed by extraction twice with 100 ml ofchloroform. The organic layer was washed twice with 100 ml of saturatedsaline and dried over anhydrous sodium sulfate. The solvent was thendistilled off, whereby 34.3 g of the crude reaction product wereobtained. The crude reaction product so obtained was purified bydistillation under reduced pressure, whereby 23.0 g of2-chloro-5-chloromethyl-1,3-thiazole were obtained.

Yield: 62.4%

Purity: 91.6%

Boiling point: 109-111C./18 mmHg

Example 15

In a reaction vessel, 26.8 g of 3-chloro-1-isothiocyanato-1-propene (a4:1 mixture of cis-form and trans-form) were charged, followed bycooling to 0° C. While the internal temperature was kept at 10° C. orlower, 28.0 g of sulfuryl chloride were added dropwise over one hour.After the completion of the dropwise addition, the temperature wasincreased up to 80° C. and heating was carried out at the sametemperature for one hour. After the reaction mixture was cooled down toroom temperature, it was poured into 200 ml of a 10% aqueous solution ofsodium carbonate. The resulting mixture was then extracted twice with200 ml of ethyl acetate. The organic layer was washed once with 100 mlof saturated saline and dried over anhydrous sodium sulfate. The solventwas then distilled off, whereby 35.2 g of the crude reaction productwere obtained. The crude reaction product so obtained was subjected todistillation under reduced pressure, whereby 16.5 g of2-chloro-5-chloromethyl-1,3-thiazole were obtained.

Yield: 45.3%

Purity: 92.6%

Boiling point: 107-109° C./17 mmHg

Reference Example 1

In a fractionating column of 50 cm height, 184 g of3-chloro-1-isothiocyanato-1-propene (a 2:3 mixture of cis-form andtrans-form) were fractionated, whereby 93.8 g oftrans-3-chloro-1-isothiocyanato-1-propene were obtained.

Recovery of trans-form: 85.0%

Purity of trans-form: 98.5%

Boiling point: 74-75° C./5 mmHg

Example 16

In a reaction vessel, 26.8 g oftrans-3-chloro-1-isothiocyanato-1-propene were charged, followed bycooling to 0° C. While the internal temperature was kept at 10° C. orlower, 28.0 g of sulfuryl chloride were added dropwise over 1.5 hours.After the completion of the dropwise addition, the temperature wasincreased up to 80° C. and heating was carried out at the sametemperature for one hour. The reaction mixture was cooled down to roomtemperature and then poured in 200 ml of a 10% aqueous solution ofsodium bicarbonate. The resulting mixture was extracted twice with 200ml of ethyl acetate. The organic layer was washed once with 100 ml ofsaturated saline, and then dried over anhydrous sodium sulfate. Thesolvent was distilled off, whereby 37.9 g of the crude reaction productwere obtained. The crude reaction product was subjected to distillationunder reduced pressure, whereby 31.8 g of2-chloro-5-chloromethyl-1,3-thiazole were obtained.

Yield: 91.2%

Purity: 96.6%

Boiling point: 108-110° C./17 mmHg

PROCESS 4

Example 17

In a reaction vessel, 26.8 g of 3-chloro-1-isothiocyanato-1-propene (a2:3 mixture of cis-form and trans-form) were charged, followed bycooling to 0° C. While the internal temperature was kept at 10° C. orlower, 28.0.g of sulfuryl chloride were added dropwise over 1 hour.After the completion of the dropwise addition, the temperature wasincreased up to 80° C. and the heating was carried out at the sametemperature for one hour. The reaction mixture was then cooled down toroom temperature and then poured in 200 ml of a 10% aqueous solution ofsodium carbonate. The resulting mixture was extracted twice with 200 mlof ethyl acetate. The organic layer was washed once with 100 ml ofsaturated saline, and then dried over anhydrous sodium sulfate. Thesolvent was distilled off, followed by simple distillation, whereby 32.7g of the crude 2-chloro-5-chloromethyl-1,3-thiazole were obtained.

Yield: 68.3%

Purity: 70.4%

Boiling point: 107-109° C./17 mmHg

Example 18

In 4 ml of hexane, 2.01 g of the crude2-chloro-5-chloromethyl-1,3-thiazole obtained in Example 17 weredissolved, followed by stirring at −20° C. for 5 minutes, whereby awhite solid was precipitated. The white solid so obtained was collectedby filtration, whereby 1.34 g of 2-chloro-5-chloromethyl-1,3-thiazole(purity: 97.0%) were obtained.

Example 19

In 4 ml of heptane, 2.03 g of the crude2-chloro-5-chloromethyl-1,3-thiazole obtained in Example 17 weredissolved, followed by stirring at −20° C. for 5 minutes, whereby awhite solid was precipitated. The white solid so obtained was collectedby filtration, whereby 1.28 g of 2-chloro-5-chloromethyl-1,3-thiazole(purity: 97.3%) were obtained.

Japanese Priority Application Nos. 33649/1996, 128694/1996, 128695/1996,129781/1996, 205885/1996, 207045/1996 and 207046/1996 are incorporatedherein by reference in their entirety.

Obviously, numerous modifications and variations of the presentinvention are possible in light of the above teachings. It is thereforeto be understood that within the scope of the appended claims, theinvention may be practiced otherwise than as specifically describedherein.

What is claimed as new and desired to be secured by letters patent ofthe United States is:
 1. A process for the preparation of2-chloro-5-chloromethyl-1,3-thiazole, which comprises reacting3-chloro-1-isothiocyanato-1-propene consisting essentially of the transisomer with a chlorinating agent.
 2. The process of claim 1, wherein thechlorinating agent is sulfuryl chloride.